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Modifying mRNA-LNPs either with antibodies or their derivatives (Ab-mRNA-LNPs) has emerged as a promising drug delivery system (DDS) due to its efficacy and target specificity. Manufacturing Ab-mRNA-LNPs, however, involves complex and multi-step procedures that include the encapsulation of mRNA followed by the anchoring of antibodies via polyethylene glycol (PEG) linker-conjugated lipids. In this work, we present a seamless strategy for the production of Ab-mRNA-LNPs by integrating the post-encapsulation of mRNA into mRNA-free LNPs (fLNPs) with a post-insertion of ligand-conjugated PEG-lipid (Lig-PEG-lipid). Using a T-cell-targeting model, we further describe how targeting efficacy is influenced by controlling the surface nature of the Ab-mRNA-LNPs either via the modification of PEG-lipids or by replacing the phospholipids. Modification of the DSPE-PEG-methoxy and employment of either DSPC or DPPC significantly improves the accumulation of Ab-mRNA-LNPs in T cells. These findings highlight the importance of LNP surface engineering.<\/jats:p>","DOI":"10.1021\/acsabm.6c00925","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T16:57:46Z","timestamp":1784825866000},"page":"7157-7166","source":"Crossref","is-referenced-by-count":0,"title":["Preparation of Antibody-Modified mRNA-LNPs via a Combination of Post-Encapsulation and Post-Insertion"],"prefix":"10.1021","volume":"9","author":[{"given":"Yoshie","family":"Ri","sequence":"first","affiliation":[{"name":"Tohoku University , , 6-3, Aoba, Aramaki, Aoba-ku , , ,","place":["Sendai city, Miyagi, Japan, 980-8578"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shion","family":"Oshima","sequence":"additional","affiliation":[{"name":"Tohoku University , , 6-3, Aoba, Aramaki, Aoba-ku , , ,","place":["Sendai city, Miyagi, Japan, 980-8578"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Tohoku University , , 6-3, Aoba, Aramaki, Aoba-ku , , ,","place":["Sendai city, Miyagi, Japan, 980-8578"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Sugawara","sequence":"additional","affiliation":[{"name":"Tohoku University , , 6-3, Aoba, Aramaki, Aoba-ku , , ,","place":["Sendai city, Miyagi, Japan, 980-8578"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizuho","family":"Hori","sequence":"additional","affiliation":[{"name":"Tohoku University , , 6-3, Aoba, Aramaki, Aoba-ku , , ,","place":["Sendai city, Miyagi, Japan, 980-8578"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siril Yves","family":"Junior","sequence":"additional","affiliation":[{"name":"Tohoku University , , 6-3, Aoba, Aramaki, Aoba-ku , , ,","place":["Sendai city, Miyagi, Japan, 980-8578"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuta","family":"Nakai","sequence":"additional","affiliation":[{"name":"NOF CORPORATION , , 3-3 Chidori-cho, Kawasaki-ku , , ,","place":["Kawasaki City, Kanagawa, Japan, 210-0865"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasumi","family":"Ito","sequence":"additional","affiliation":[{"name":"NOF CORPORATION , , 3-3 Chidori-cho, Kawasaki-ku , , ,","place":["Kawasaki City, Kanagawa, Japan, 210-0865"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuto","family":"Shimoya","sequence":"additional","affiliation":[{"name":"Tohoku University , , 6-3, Aoba, Aramaki, Aoba-ku , , ,","place":["Sendai city, Miyagi, Japan, 980-8578"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Sakurai","sequence":"additional","affiliation":[{"name":"Tohoku University , , 6-3, Aoba, Aramaki, Aoba-ku , , ,","place":["Sendai city, Miyagi, Japan, 980-8578"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6262-2436","authenticated-orcid":true,"given":"Hidetaka","family":"Akita","sequence":"additional","affiliation":[{"name":"Tohoku University , , 6-3, Aoba, Aramaki, Aoba-ku , , ,","place":["Sendai city, Miyagi, Japan, 980-8578"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"issue":"11","key":"2026080308062693300_cit1","doi-asserted-by":"publisher","first-page":"16982","DOI":"10.1021\/acsnano.1c04996","article-title":"Lipid Nanoparticles From Liposomes to MRNA Vaccine Delivery, a Landscape of Research Diversity and Advancement","volume":"15","author":"Tenchov","year":"2021","journal-title":"ACS Nano"},{"issue":"28","key":"2026080308062693300_cit2","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202310531","article-title":"Lipid Nanocarrier-Based MRNA Therapy: Challenges and Promise for Clinical Transformation","volume":"20","author":"Li","year":"2024","journal-title":"Small"},{"issue":"9","key":"2026080308062693300_cit3","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1038\/s41573-024-00977-6","article-title":"The 60-Year Evolution of Lipid Nanoparticles for Nucleic Acid Delivery","volume":"23","author":"Cullis","year":"2024","journal-title":"Nat. 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